Confinement of liquids on surfaces

ABSTRACT

A microfluidic device for applying a liquid to a surface comprises a chamber for carrying the liquid, an aperture in the chamber for communicating liquid from the chamber to the surface via a conduit having outer sides of limited wettability to the liquid. This device provides a solution for confining liquids to defined areas of a surface without involving physical seals and additionally permits moving the device and confined liquid on the surface.

The present invention generally relates to confinement of liquids onsurfaces and particularly relates to methods and apparatus for applyingand confining liquids to surface areas.

There are many applications in which it is desirable to apply a liquidto a surface. An example of such an application is in patterning orother processing of surfaces. Patterning and processing of surfaces withliquids is becoming increasingly important in a range of fields,including chemistry, biology, biotechnology, materials science,electronics, and optics. Patterning a surface by applying a liquid tothe surface typically involves confinement of the liquid to definedregions of the surface.

A surface is typically wettable by a liquid if the contact angle betweena drop of the liquid and the surface is less than 90 degrees. A channelfor carrying a liquid is typically wettable if the channel exerts anegative pressure on the liquid when partially filled. Such a negativepressure promotes filling of the channel by the liquid. In a channelhaving a homogeneous surface, a negative pressure arises if the contactangle between the liquid and the surface is less than 90 degrees. Asurface is typically regarded as more wettable if the contact anglebetween the surface and the liquid is smaller and less wettable if thecontact angle between the surface and the liquid is higher.

One conventional surface patterning technique is lithography. Inlithography, a mask is usually applied to the surface to be patterned.Apertures are formed in the mask to define regions of the surface to beexposed for treatment. Those areas of the surface remaining covered bythe mask are protected from treatment. The mask is typically formed froma patterned layer of resist material. The surface carrying the mask isthen typically immersed in a bath of chemical agents for treating theexposed regions of the surface. Lithography is a relatively expensiveprocess to perform, involving multiple steps, expensive instruments andlaboratory facilities with controlled environments. With the possibleexception of in situ synthesis of short DNA strands, lithography isgenerally unsuitable for handling and patterning biomolecules onsurfaces. Lithography is also unsuitable for simultaneously processingsurfaces with different chemicals in parallel, as described byWhitesides, Annu. Rev. Biomed. 3 (2001). 335-373. There can beincompatibility between different process steps or chemicals used inlithography and between various surface layers processed by lithography.

Another conventional surface patterning technique is drop delivery. Dropdelivery systems, such as pin spotting systems, ink jet systems, and thelike, typically project a relatively small volume of liquid onto aspecific location on a surface. See Shena, M., “Microarray biochiptechnology”. Eaton Publishing 2000. However, these systems have limitedresolution due to spreading of dispensed drops on the surface.Additionally, the quality of patterns formed by such systems is stronglylimited by drying of the delivered liquid, as described by Smith, J. T.,“Spreading Diagrams for the Optimization of Quill Pin Printed MicroarrayDensity”, Langmuir, 18 (2002), p 6289-6293. These systems are notgenerally useful for dissolving or extracting materials from a surface.Additionally, these systems do not facilitate a flow of liquid over asurface. Furthermore, these systems are not suited to process a surfacesequentially with several liquids.

PCT WO 01/63241 A2 describes a surface patterning technique involving adevice having a channel with a discharge aperture. A matching pillar isengaged with the discharge aperture to promote deposition of moleculeson the top surface of the pillar. A disadvantage with this device isthat it is not possible to vary patterning conditions for differentpillars individually.

Exposure of the surface to the liquid needs to be sufficiently long toallow reagents to reach the surface by diffusion. The method alsorequires a surface with pillars matching the aperture. Precise alignmentof the device with the pillars before engagement is required. Spacingbetween the discharge aperture and the pillars needs external control.The pillars cannot be moved on the surface to draw lines.

Yet another conventional surface patterning technique involvesapplication of a microfluidic device to the surface. An example of sucha device is described in U.S. Pat. No. 6,089,853. The device describedtherein can establish a flow of liquid over a surface. The flow can becreated via capillary action in the device. The device can treat asurface with different liquids in parallel. However, the device must besealed to the surface in the interests of confining the liquid to theregion of the surface to be treated. Such confinement allows theformation of patterns with relatively high contrast and resolutions.These are desirable qualities where biomolecules are patterned on asurface for biological screening and diagnostic purposes. In addition,the device must be placed on the surface to be treated and sealed aroundthe processing regions before it can be filled with treatment liquid. Ifthe flow is created by capillary action, other problems arise. Forexample, service ports in the device must be filled with treatmentliquid for each patterning operation. In addition, only one liquid canbe delivered to each channel in the device. The liquid cannot be flushedout of the channels before separation of the device from the surface.Furthermore, the treatment liquid tends to spread away from the regionsof the surface to be treated during removal of the device from thesurface. Also, the device is not suitable for processing a surfacesequentially with several liquids. If the flow is created by externalactuation, such as pressurization, electric fields, or the like, thenother problems arise. For example, an individual connection from theactuator must be made to each channel in the device. Such connections toperipheral equipment limit the density of channels that can beintegrated into the device and individually addressed. Pumping, valving,and control complexity increases as the number of channels increases.External connections create dead volume between the device and externalactuators because of the intervening conduits.

Another microfluidic device for localized processing of a surface isdescribed in IBM Technical Disclosure Bulletin reference RD n446 Article165 Page 1046. This device is similar to that described in U.S. Pat. No.6,089,853. The device permits several liquids to be flushed in sequenceover the same surface area without requiring separation of the devicefrom the surface. Such a device is thus useful for chemical andbiological reactions involving the sequential delivery of severalliquids. A disadvantage associated with this device however is that itmust be sealed around the region of the surface to be treated beforefilling. Another disadvantage is that the liquids cannot be filled priorto application on the device to the surface. Each additional steprequires supplementary filling of the relevant liquid. The lines need tobe prestructured in the device via lithography and cannot be readjustedsubsequently.

Another conventional device for confining liquids to a predefinedpattern between a top and bottom surface without involving a seal isdescribed in European Patent 0 075 605. This device is useful forperforming optical analysis of a liquid trapped between the top andbottom surface. However, the device requires predefined topographical orchemical patterns on both the top and bottom surfaces. Also, the device,having no inlet or outlet ports, is not suitable for the transport ofliquids.

Another device for guiding liquids along a predetermined path isdescribed in WO 99/56878. This device can flow several liquidssimultaneously over a surface without involving seal to confine theliquids. However, a disadvantage of this device is that separation gapsbetween paths have to be capillary inactive. This limits path sizes togreater than 1 mm. Otherwise, meniscus pressures produce uncontrolledspreading of liquid. Another disadvantage of this device is that liquidis not retained after separation and can instead spread over thesurface. A further disadvantage of this device is that liquid deliveryrequires an external connection to each path. Cumbersome peripheral flowcontrol devices are also required.

Yet another method for guiding liquid along a surface without involvinga seal is described in Zhao et al., Science, Vol. 291 (2001), p.1023-1026. Here, the surface is patterned with a wettability pattern.Specifically, two wettable paths mirroring each other are defined onotherwise non-wettable top and bottom surfaces. This produces “virtual”channels without lateral walls that can have micrometer width. Adisadvantage of this method is that it requires wettability patterns onboth the top and bottom surfaces. In other words, the path for the flowof liquid must be predetermined using lithography, which is expensiveand lacks flexibility. Furthermore, the flow paths cannot be readjustedsubsequently. Additionally, the wettability contrast between the twopatterns needs to be very high, and requires both non-wettable areas onthe top and bottom surfaces and highly wettable areas within the virtualchannel. Furthermore, the two patterns have to match each other exactlyin shape and alignment. Capillary action can be used to fill thechannels, but the liquid cannot be removed or exchanged. This method isalso susceptible to uncontrolled spreading of liquid because it isrelatively difficult to produce sufficiently non-wettable surfaces.

It would be desirable to provide a technique for confining a liquid on asurface in a more versatile and convenient manner. In accordance withthe present invention, there is now provided a device for applying aliquid to a substrate surface, the device comprising a chamber forcarrying the liquid, an aperture in the chamber for communicating liquidfrom the chamber to the substrate surface via a conduit having outersides of limited wettability to the liquid.

Liquid dispensed from the device is confined in a volume defined by theaperture. A physical seal between the device and the substrate surface,that is, the surface to be contacted by the liquid, is not needed. Inpreferred embodiments of the present invention, the confinement arisesthrough the geometry of the aperture and the superposition of awettability pattern on the aperture and surrounding regions of thedevice. Such devices are especially although not exclusively useful inthe application of surface treatment in the a range of fields, includingmicroelectronics, optics, biology, biochemistry, and biotechnology. Thepresent invention also extends to an array of such devices.

In a particularly preferred embodiment of the present invention, thedevice has a body including a protrusion defined by the outer sides ofthe conduit. The conduit preferably comprises inner sides wettable bythe liquid. The body preferably comprises a plane inner surfacesurrounding the protrusion and a plane outer surface parallel to, offsetfrom, and surrounding the inner surface, the protrusion extending fromthe inner surface and having an end coplanar with outer surface. Theinner surface may form a peripheral recess surrounding the protrusion.The outer surface is preferably of limited wettability to the liquid.The end of the protrusion is preferably wettable by the liquid. In someembodiments of the present invention, the outer surface may define aplane located between that defined by the inner surface and that definedby the end of the protrusion. In other embodiments of the presentinvention, the outer surface may be omitted altogether.

In a preferred embodiment of the present invention, the devicecomprises: a first chamber for carrying the liquid; a second chamber forcarrying the liquid; a first aperture in the first chamber forcommunicating liquid from the first chamber to the substrate surface viaa first conduit having outer sides of limited wettability to the liquid;and, a second aperture in the second chamber for communicating liquidfrom the second chamber to the substrate surface via a second conduithaving outer sides of limited wettability to the liquid. The devicepreferably comprises a body including a protrusion defined by the outersides of the first and second conduits. The first and second conduitsmay comprise inner sides wettable by the liquid. The body may comprise aplane inner surface surrounding the protrusion and a plane outer surfaceparallel to, offset from, and surrounding the inner surface, theprotrusion extending from the inner surface and having an end coplanarwith outer surface. The inner surface may form a peripheral recesssurrounding the protrusion. The outer surface may be of limitedwettability to the liquid. The end of the protrusion is preferablywettable by the liquid.

In one application, pressure in the chamber can be regulated such thatliquid is retained in the chamber when the aperture is remote from thesubstrate surface. When the aperture is proximal to the substratesurface, pressure may be applied to initiate flow of liquid out of theaperture onto the surface. When the device is withdrawn from thesurface, the pressure may be tuned to draw back excessive liquid fromthe surface. There may be a plurality of chambers each coupled to anaperture, where the pressure is controlled in each chamber, in parallelor individually.

The chamber pressure may be generated by external pumps such as syringepumps or peristaltic pumps or other means of pressurization, byintegrated pumps such as microfabricated pumps, by electro-kineticpumping, by capillary-force based pumping, or by other pumping means.Further, there may be provided valves for controlling flow of liquid.Such valves may be located within external connections, in the chamber,in connections between chamber and aperture, or in the aperture. Suchvalves may be closed or opened on demand. Devices embodying the presentinvention may form or otherwise constitute a fluidic network. There maybe a feedback system for measuring pressure within such a network, forexample at apertures and/or chambers. Alternatively, there may beprovided feedback based on the volume of liquid pumped. The feedback mayfacilitate control of flow of liquid and avoid undesired spreading ofliquid on the substrate surface. There may be a plurality of chamberseach coupled to an aperture, where pressure is controlled in eachchamber, in parallel or individually. Further, there may be one or morevalves that control the flow for each chamber in parallel orindividually.

The chamber may apply a pressure for retaining the liquid when theaperture is remote from the substrate surface. The chamber may comprisea capillary network for applying pressure to the liquid. The capillarynetwork may comprise at least one of a plurality of parallel capillarymembers, a mesh, a porous material, and a fibrous material. There may bea plurality of chambers each coupled to an aperture. The pressures maybe such that the liquid is drawn towards the chambers in response towithdrawal of the aperture from the substrate surface. There may be aplurality of first and second chambers each coupled to the aperture,where the pressure is controlled in each chamber, in parallel orindividually.

The end of the protrusion may comprise a flow path extending from afirst aperture to a second aperture connected to a first chamber and asecond chamber respectively. The protrusion defining the flow path maybe flat, or rounded, or contain a recess of rectangular of curved crosssection.

Pressure in the first chamber may be regulated such that liquid isretained in the first aperture when the flow path is remote from thesubstrate surface. Pressure in the second chamber may also be regulatedsuch that the difference between the first and second pressures isoriented to promote flow of the liquid from the first chamber to thesecond chamber via the flow path when the flow path is located proximalto the substrate surface with the liquid in the device contacting thesubstrate surface. The first and second pressures can further beregulated such that excessive liquid is drawn towards at least thesecond chamber in response to withdrawal of the flow path from thesubstrate surface. There may be a plurality of first chambers eachcoupled to the flow path. Equally, there may be a plurality of secondchambers each coupled to the flow path.

The pressure in the first and second apertures may be generated byexternal pumps or the like as herein before described. There may beprovided a feedback system that measures the pressure within the system,for example at the first and second apertures and/or the first andsecond chambers. The feedback may be based on the volume of liquidpumped in the first and second chambers. The feedback may facilitate thecontrol of the flow of liquid and avoid undesired spreading of liquid onthe substrate surface. There may be a plurality of first and secondchambers each coupled to first and second apertures, where pressure iscontrolled in each of the first and second apertures, in parallel orindividually. Further, there may be one or more valves controlling flowfor each of the first and second apertures in parallel or individually.There may be a plurality of first chambers each coupled to the flowpath. Equally, there may be a plurality of second chambers each coupledto the flow path.

In an example of the present invention, the first chamber applies afirst pressure for retaining the liquid when the flow path is remotefrom the substrate surface. The second chamber applies a second pressureto the liquid such that the difference between the first and secondpressures is oriented to promote flow of the liquid from the firstchamber to the second chamber via the flow path in response to the flowpath being located proximal to the substrate surface and the liquid inthe device contacting the substrate surface. The first and secondpressures are such that the liquid is drawn towards at least the secondchamber in response to withdrawal of the flow path from the substratesurface. At least one of the first chamber and the second chamber maycomprise a capillary network for applying pressure to the liquid. The oreach capillary network may comprise at least one of a plurality ofparallel capillary members, a mesh, a porous material, and a fibrousmaterial. There may be a plurality of first chambers each coupled to theflow path. Equally, there may be a plurality of second chambers eachcoupled to the flow path. The first and second pressures may be suchthat the liquid is drawn towards the first chamber and the secondchamber in response to withdrawal of the flow path from the substratesurface.

Many other applications of the present invention are possible.

Devices embodying the present invention may be of unitary construction,possibly formed from any one of elastomer, silicon, SU-8, photoresist,thermoplastic, ceramic, and metal. Alternatively, devices embodying thepresent invention may be of layered construction, with each layerpossibly formed from any one of glass, polymer, silicon, SU-8,photoresist, thermoplastic, metal, and ceramics.

Viewing the present invention from another aspect, there is now provideda method for applying a liquid to a substrate surface, the methodcomprising: locating a single aperture device as herein before describedproximal to the substrate surface; supplying the liquid to the substratesurface via the device; and, retracting the device from the substratesurface.

Viewing the present invention from yet another aspect, there is nowprovided a method for applying a liquid to a substrate surface, themethod comprising: locating a two aperture device as herein beforedescribed proximal to the substrate surface; supplying the liquid to thesubstrate surface via the device; flowing the liquid from the firstchamber to the second chamber via the flow path; and, retracting thedevice from the substrate surface. The flow of the liquid from the firstchamber to the second chamber may be varied during the supply of theliquid to the surface.

Prior to the retracting, devices as herein before described may be movedrelative to the substrate surface with the liquid in the or eachaperture contacting with the substrate surface.

The present invention also extends to a method for applying a liquid toa substrate surface, comprising: locating a multiple aperture device asherein before described proximal to the substrate surface; supplying theliquid to the substrate surface via the device; moving the devicerelative to the substrate surface with the liquid in each aperturecontacting with the substrate surface; and, retracting the device fromthe substrate surface. The device may be oriented relative to thesubstrate surface such that traces of the liquid produced as the deviceis moved relative to the substrate surface remain separate. Similarly,the device may be oriented relative to the substrate surface such thattraces of the liquid produced as the device is moved relative to thesubstrate surface overlap. Prior to locating, a similar liquid may beloaded into the chambers. Alternatively, different liquids may be loadedinto the chambers.

The present invention further extends to a method for applying a liquidto a substrate surface, comprising: locating an array of two aperturedevices as herein before described proximal to the substrate surface;supplying the liquid to the substrate surface via the array; in eachdevice of the array, flowing the liquid from the first chamber to thesecond chamber via the flow path; moving the array relative to thesubstrate surface with the liquid in each aperture contacting with thesubstrate surface; and, retracting the array from the substrate surface.In at least one device of the array, the flow of the liquid from thefirst chamber to the second chamber may be varied during the supply ofthe liquid to the surface. The array may be oriented relative to thesubstrate surface such that traces of the flows of liquid produced asthe array is moved relative to the substrate surface remain separate.Similarly, the array may be oriented relative to the substrate surfacesuch that traces of the flows of liquid produced as the array is movedrelative to the substrate surface overlap. Similar or different liquidsmay be loaded into each device of the array.

In one embodiment of the present invention, a single chamber device asherein before described, is brought close to a surface so as to contactthe surface with the liquid in an area of micrometer dimensions definedby the geometry of the aperture. The device is then removed from thesurface. In another embodiment of the present invention, prior toremoval of the device, the surface is laterally moved relative to thedevice with the liquid in the device remaining in contact within thesurface so that the liquid is traced across the surface. In yet anotherembodiment of the present invention, the tracing is performed using thetwo aperture device herein before described, with the liquid flowingbetween the apertures as the device is traced is over of the surface.

As indicated earlier, devices embodying the present invention areparticularly useful for transporting liquid from a chamber, well,reservoir, or similar container, to a surface, and to confine the liquidon the surface without need for a physical seal. Thus, the or eachaperture of such device may be defined by non-sealing materials such assilicon or the like. The non-contact operation of devices embodying thepresent invention prevents contamination or other damage to the surfacebeing treated and to the device.

Treatment techniques embodying the present invention are applicable tosurfaces having wide range of different properties and wettability. Thetwo aperture device herein before described permits addition of a flowof liquid, thus preventing depletion of material adsorbed to the surfacetreated. Homogeneous patterns of, for example, biomolecules may bethereby produced. When a device embodying the present invention istraced over the surface treated, the lines produced may be smoother thanthose possible with conventional techniques, such as ink jet printing.Because the liquid deposited is relatively small, there is no spreading,drying is quick, and does not lead to excessive accumulation of materialon the surface, such lines may be made smaller than possible withconventional techniques.

If a flow is applied, via a two aperture device as herein beforedescribed, the concentration of deposited materials may be varied as thedevice is drawn of the surface treated. A range of gradients inconcentration may be thus produced, depending on application. Such adevice is useful for both additive and subtractive patterning ofmaterials onto a surface. A series of such devices may drawn over asurface in sequence. Each aperture of such devices may contain adifferent one of a group of reagents for collectively implementing achain reaction on the surface.

Another advantage associated with devices embodying the presentinvention is that they can be pre-filled with processing liquids forsubsequent repetitive application and removal from areas of surfaces tobe processed. Surface processing can be repeated multiple times from thesame device without refilling and thus delay. Yet another advantageassociated with such devices is that they can be swiftly mass producedvia conventional microfabrication techniques. In typical applications, adevice embodying the present invention can be placed at an arbitrarylocation on a surface and process parameters can be controlled viadimensions and contact time. Arrays of such devices are relatively easyto fabricate.

Another advantage associated with devices embodying the presentinvention is that they can be used to treat curved surfaces such asbeads or cylinders, inhomogeneous surfaces, surface with variablewettability, corrugated or otherwise roughened surfaces and the like.

Devices embodying the present invention may be employed to depositbiomolecules in selected regions of a surface to make bio-arrays, thusfacilitating mass fabrication of bio-chips. Devices embodying thepresent invention can be equally employed in subjecting selected areasof a surface to other processes, such as processes for: repairingpattern defects on a surface; etching specific areas of a surface;depositing metal on a surface; localizing an electrochemical reactionson a surface; depositing catalytic particles for electroless depositionof metals, deposition glass or latex beads or other particles on asurface; passivating specific areas of a surface; patterning proteins,DNA, cells, or other biological entities on a surface; making assays;and, staining cells.

Preferred embodiments of the present invention will now be described, byway of example only, with reference to the accompanying drawings, inwhich:

FIG. 1 is a cross sectional side view of a device embodying the presentinvention;

FIG. 2 is a plan view of a bottom surface of the device shown in FIG. 1;

FIG. 3 is a cross sectional side view of the device shown in FIG. 1 inoperation;

FIG. 4 is a plan view of a bottom surface of the device shown in FIG. 1in operation;

FIG. 5 is a cross sectional side view of another device embodying thepresent invention;

FIG. 6 is a plan view of a bottom surface of the device shown in FIG. 5;

FIG. 7 is a cross sectional end view of yet another device embodying thepresent invention;

FIG. 8 is a plan view of a bottom surface of the device shown in FIG. 7;

FIG. 9 is a cross sectional side view of the device shown in FIG. 7 inoperation;

FIG. 10 is a plan view of a bottom surface of the device shown in FIG. 7in operation;

FIG. 11 is a cross sectional end view of yet another device embodyingthe present invention;

FIG. 12 is a plan view of a bottom surface of the device shown in FIG.11 in operation;

FIG. 13 is a plan view of the device shown in FIG. 1 operating in adrawing mode;

FIG. 14 is a plan view of a surface treated by the drawing operationshown in FIG. 13;

FIG. 15 is a plan view of the device shown in FIG. 5 operating in adawning mode;

FIG. 16 is a plan view of a surface treated by the drawing operationshown in FIG. 15;

FIG. 17 is a plan view of the device shown in FIG. 7 operating in adrawing mode; and,

FIG. 18 is a plan view of a surface treated by the drawing operationshown in FIG. 17; and,

FIG. 19 is a cross section side view of another device embodying thepresent invention in operation.

Referring first to FIGS. 1 and 2 in combination, an example of a deviceembodying the present invention comprises a body 10 formed from amaterial such as PDMS, silicon, SU-8, photoresist, polymers, ceramicsand metals. A chamber 20 is formed on one side of the body 10. Thechamber 20 connects to an aperture 30 open to the other side of the body10 via a necked portion 40 or channel. The aperture 30 is formed in aprotrusion 50 extending from a plane inner surface 60. The interiorwalls of the chamber 20, the interior walls 70 of the aperture 30 andthe end 80 the protrusion 50 are wettable by the liquid. The exteriorwalls 90 of the protrusion 50 and the inner surface 60 are non-wettable.In other embodiments of the present invention, the end 80 may benon-wettable. The protrusion 50 is surrounded by the inner surface 60.In turn, the inner surface 60 is surrounded by a non-wettable planeouter surface 100 parallel to the inner surface 60. The inner surface 60and its interior walls 95 are non-wettable. The outer surface 100 andthe end 80 of the protrusion 50 are coplanar, so that the inner surface60 resides in a recess surrounding the aperture 30.

Different techniques may be employed to apply surface wettabilitypatterning to the device. For example, surfaces to be made non-wettablemay be inked via a stamp with a thiol having a non wettable end group.Surfaces to be made wettable may be exposed to a thiol having a wettableend group in solution. The solvent may be ethanol, for example.Temporary PDMS sealing may be employed to mask applications ofwettability and non-wettability agents from each other. The ink may beapplied via a stamp. In other examples, both the wettability and nonwettability agents may be supplied in solution. The geometry of thedevice may provide a capillary network to guide such agents to desiredsurfaces of the device. The surfaces may be pretreated with a primerlayer of gold or similar noble metal. Such a primer layer may be appliedby evaporation, sputtering, or the like.

Referring now to FIGS. 3 and 4 in combination, in operation, the chamber20 is loaded with a liquid 110 to be dispensed onto a surface 120 to betreated. The surface 120 may be a glass surface. However, the surface120 may have other forms The surface 120 can be flat, rough, corrugated,porous, fibrous, and/or chemically inhomogeneous. The liquid 110 isretained in the chamber 20 by the combined action of surface tension atthe aperture 30 and pressure in the chamber 20. The pressure in thechamber 20 is preferably set to negative values, P<0. This contributesto retaining liquid 110 in the chamber 20. The aperture 30 provides acapillary or meniscus pressure exerting a negative pressure OP<0 onliquid 110. If one likes to keep the aperture filled with liquid, he cantune P such as OP<P. OP then sucks liquid 110 from the chamber 20 intoaperture 30. Aperture 30 widens at its intersection with the end 80,thereby suppressing the capillary pressure. P may even be greater thanor equal to 0, in which case the aperture 30 is overfilled with liquid110. This leads to liquid 110 having a convex surface. Such a surface isa source of positive pressure albeit of relatively low magnitude. Insuch a case, aperture 30 is filled with liquid 110 up to theintersection with the end 80. Relatively small dimensions of aperture 30are desirable for forming relatively high curvatures in the surface ofliquid 110. By virtue of tension between liquid 110 and the surroundingmedium, such curvatures produce relatively high pressures that canconfine liquid 110 within aperture 30 despite a positive pressure head.

In operation, the aperture 30 is brought proximal to the surface 120. Bytuning the pressure P in the chamber 20, the liquid fills the aperture40 so that the liquid 110 contacts the surface 120. The non-wettablewalls 90 and 95, the recessed inner surface 60, and non-wettable outersurfaces 100 cooperate to confine the liquid 110 contacting the surface120 to an area of the surface 120 commensurate with the cross-sectionalwidth of the aperture 30. Contact between the surface 120 and liquid 110can be curtailed applying a pressure P to the chamber to aspirateexcessive liquid from the surface, and by simultaneously or subsequentlydisengaging the device from the surface 120. Liquid contacts 110 may bemay be made and broken by alternately engaging and disengaging thedevice with the surface 120.

In operation active flow controllers such as external pumps, integratedpumps, and valves may be provided to regulate the pressure P in thechamber 20.

A plurality of a capillary members may extend into the chamber 20 andact as flow controller. The capillary members form a capillary networkexerting capillary action on the liquid 110. The capillary members mayhave circular, hexagonal, square, rectangular, or other cross sections.Alternatively, the flow controllers may each comprise a different formof capillary network, such as a network formed from mesh, porous, orfibrous material.

The supply of liquid 110 can be replenished as necessary via thechamber. Such replenishing permits repetitive reuse of the device. Thechamber may be loaded and/or unloaded with liquid 110 from below via theaperture 30. A lid may be provided to close the chamber. The lid may bepermanently sealed so that liquid 110 can only be introduced via theaperture 30. The apertures 30 may be likewise provided with a lid toprevent evaporation during periods of nonuse. A support device having areservoir for liquid 110 may be provided for filling, refilling, anddraining the chamber without involving removal of lids.

Liquid 110 may contain treatment agents for processing a region of thesurface 120. Engaging the device with the surface 120 causes exposure ofthe region of the surface 120 facing the end 80 to the treatment agent.The treatment agent may comprise molecules. The device is thereforeuseful in bio-patterning applications. However, other applications arepossible, such as sequential delivery of different treatments to thesurface 120. Similarly, other liquids may be employed depending on thesurface processing desired. Examples of possible liquids includeetchants and the like for producing localized chemical reactions on thesurface 120.

The body 10 may be formed from elastomeric or rigid materials. Suchmaterials can be shaped by microfabrication techniques such asphotolithography, etching, injection molding and the like. The body 10may be unitary in construction or an assemblage of parts such as alayered assembly. Each layer may formed from a different material suchas elastomer, silicon, SU-8, photoresist, thermoplastics, ceramic, andmetal.

A manipulator may be employed to position the device relative to thesurface 120. The manipulator may be manually controlled or automaticallycontrolled via a programmable computer or similar electronic controlsystem. The manipulator may act on the device, the surface 120, or both,providing control of in plane and/or out of plane translational and/orrotational relative motions.

A plurality of devices as herein before described with reference toFIGS. 1 to 4 may be ganged together in an array. For example, referringto FIGS. 5 and 6 in combination, such an array may comprise twoapertures 31 and 32 extending from separate chambers. Each chamber maycontain the same liquid or different liquids. Other arrays may comprisemore than two apertures. Groups of such apertures may share a commonchamber.

With reference to FIGS. 7 and 8 in combination, in another embodiment ofthe present invention, the apertures 31 and 32 are interconnected via anintervening flow path 130. The apertures 31, 32, and the flow path 130are together formed in the protrusion 50 from the inner surface 60. Theflow path 130 and the end 80 of the protrusion 50 are substantiallycoplanar. The interior walls of the chambers 20, the interior walls 70of the apertures 31, 32, the end 80 of the protrusion 50, and the flowpath 130, are wettable by the liquid. Again, the exterior walls 90 ofthe protrusion 50 are non-wettable. The protrusion 50 is surrounded bythe inner surface 60. In turn, the inner surface 60 is surrounded by thenon-wettable outer surface 100. The outside walls 95 that connect theinner surface 60 to the outer surface 100 may be non-wettable too. Theouter surface 100 and the end 80 of the protrusion 50 are coplanar, sothat the inner surface 60 resides in a recess surrounding the apertures31, 32 and the flow path 130. The flow path 130 may be straight orcurved. The flow path 130 may include a recess formed between theapertures 31 and 32 of rounded or rectangular cross section. Inoperation, the chamber 20 connected to aperture 31 acts as a fill portand the chamber 20 connected aperture 32 acts as a flow promotion port.The liquid 110 is initially introduced to the fill port.

Referring to FIGS. 9 and 10 in combination, in operation, the fill portholds liquid 110 at pressure P1. P1 is preferably negative. P1<0. Thiscontributes to retaining liquid 110 in the fill port. Aperture 31 fromthe fill port provides a capillary or meniscus pressure exerting anegative pressure OP1<0 on liquid 110.

A tip (not shown) wettable to the liquid 110 may extend from the body 10into the flow path 40 adjacent aperture 31. The tip sucks up the liquid110 to its end by capillary force. The tip may be resilient to preventdamage to the device or the surface 120. There may be multiple tipsspaced along the flow path 40 to ensure uniform spacing between the flowpath 40 and the surface 120.

Engagement of the device with the surface 120 creates a surface channelcorresponding to the flow path 130. If provided, tips inside and outsideof the flow channel abut the surface 120 to define the size of thesurface channel, together with the flow path 130. The pressure P1initiates the flow of liquid by expelling the liquid from the aperture31 into the flow path 130. P1 is tuned so that the liquid enters theflow path 130 but does not spread out on the surface. The depth of thesurface channel, the interfacial tension of the liquid, the contactangle of the liquid on the substrate surface and on the outer walls 90define the maximal pressure head that the channel can withstand.Further, the surface channel generates a capillary pressure CP on theliquid 110 while the liquid 110 fills the surface channel from theaperture 31 to the aperture 32. For a capillary pressure CP<1, CP willhelp propel the liquid from the aperture 31 to the aperture 32. Themagnitude of CP is determined by the surface tension of liquid 110, thecontact angles of liquid 110 with the flow path 130 and the surface 120,and the size of the gap formed between the flow path 130 and the surface120. CP may be tuned by varying the size of the gap between the surface120 and the device. The smaller the gap, the higher the magnitude of CP.Having a wettable surface channel 130 will help lowering CP to small andnegative values.

When the liquid 110 reaches and covers the aperture 32, the liquid 110is subjected to the pressure P2 in the flow promotion port. Further, theliquid is also subjected to the capillary pressure of the aperture 32,OP2. If the walls of the aperture 32 are wettable, OP2<0, and OP2 willhelp suck the liquid into aperture 2. Thus, when liquid 110 reachesaperture 32, it is drawn into aperture 32 and propelled towards thepromotion port. In turn, the promotion port exerts a pressure P2<P1 onliquid 110. Thus, P2 supports a flow of liquid 110 from the fill port tothe promotion port. The flow rate is a function of the ratio (P1-P2)/Fr,where Fr is the flow resistance of the flow path from fill port to flowpromotion port for the liquid 110.

If the gap increases, the magnitude of CP reduces. By applying a slightnegative pressure in at least one of fill port and flow promotion port,the liquid 110 is sucked into at least one of the apertures 31, 32 anduncontrolled spreading of the liquid 110 on the substrate surface 120can be effectively prevented. The drainage causes disruption of the flowof liquid 110.

In another application, the flow of liquid is automatically started whenthe device is engaged with the surface 120. The surface channel providesa capillary pressure, CP. CP propels liquid 110 from aperture 31 toaperture 32. CP<P1 and CP<0. The magnitude of CP is determined by thesurface tension of liquid 110, the contact angles of liquid 110 with theflow path 130 and the surface 120, and the size of the gap formedbetween the flow path 130 and the surface 120. CP may be tuned byvarying the size of the gap between the surface 120 and the device. Thesmaller the gap, the higher the magnitude of CP.

Aperture 32 provides a capillary or meniscus pressure. This pressureexerts a negative second pressure OP2<0 on liquid 110 in the flow path130. OP2<P1. Thus, when liquid 110 reaches aperture 32, it is drawn intoaperture 32 and propelled towards the promotion port. In turn, thepromotion port exerts a negative pressure P2<0 on liquid 110. P2<P1.Thus, P2 supports a flow of liquid 110 from the fill port to thepromotion port. The flow rate is a function of the ratio (P1-P2)/Fr,where Fr is the flow resistance of liquid 110. Capillary pressureretains liquid 110 in the flow path 130.

If the gap increases, the magnitude of CP reduces. Eventually, CPreaches a threshold value. Below the threshold value, liquid 110 in theflow path 130 drains first into the fill port, and then, provided thatP1<0, into the promotion port. The drainage causes disruption of theflow of liquid 110. The flow of liquid 110 can be curtailed simply bydisengaging the device from the surface 120. Flow of liquid 110 can bealternatively initiated and stopped by alternately engaging anddisengaging the device with the surface 120.

The tip may be omitted and flow initialization effected by othertechniques. For example, flow initialization may be effected by firstbringing the end 80 into contact with the surface 120 so that liquid 110contacts and wets the surface 120. The device is then withdrawn from thesurface 120 to a distance equal to the desired depth of surface channel.Capillary pressure then transports liquid 110 along the flow path 130until the liquid reaches the promotion port, whereupon the pressuredifference between the ports maintains the flow. Flow initialization mayalso be achieved by locating the device close to the surface 120 in ahumid environment. The device and/or the surface may be initially cooledto promote condensation, thereby further stimulating flow.Alternatively, an electric field may be applied between the device andthe surface in the interests of stimulating liquid 110 in aperture 31 tocontact the surface 120. Similarly, a pressure pulse may be applied toliquid 110 in aperture 31 to stimulate contact with the surface 120.Alternatively, a heat pulse may be applied to the liquid 110 toinitialize the flow of liquid 110 via vaporization of the liquid 110.

The flow path 130 may have a curved cross section to prevent unwantedliquid retention, and residual flows between the chambers.Alternatively, the flow path 130 may have a rectangular cross section.This may lead to residual flow along corners of the flow path 130 whenseparated from the surface 120. Such residual flows may preventconcentration of reagents by evaporation of liquid 110. The capillarypressure of the flow path 130 when remote from the surface 120 can beoptimized by tuning wettability and geometry together with P1 and P2 toprevent unwanted liquid retention and to limit the residual flow to adesired value.

The direction of flow of liquid 110 may be selectively reversed byselectively reversing the pressure difference between the fill andpromotion ports. Specifically, P1 may be selectively made greater inmagnitude than P2. The flow path 130 can be filled with liquid 110 evenif the device is slightly tilted relative to the surface 120. The devicemay be operated facing upwardly towards a downwardly facing surface,especially where device dimensions are very small, such that forces inthe liquid interface exceed inertial forces. In general, gravity haslimited effect on the device so that use in reduced gravity environmentsis possible.

Confinement of the liquid 110 on the surface 120 is achieved viageometry and wettability of the device. The end 80 of the protrusion 50facing the surface 120 is made more wettable by liquid 110. However,side walls 90 of the protrusion 50 are made less wettable by liquid 110.There is no spread of liquid 110 because of the right angle between theside walls 90 and the surface 120 and because of the reduced wettabilityof the side walls 90. This confines the liquid 110 on the surface 120 toan area roughly corresponding to the area of the end 80 of theprotrusion 50.

The flow path 130 is around 100 micrometers long and 100 micrometerswide. Likewise, the apertures 30-32 may be around 100 micrometers wide.The surface channel may be between around 1 and 10 micrometers deep. Thevolumes of the chambers may be around 500 nanoliters each. The depth ofthe surface channel cannot exceed the width of the surface channel. Themaximum depth of the surface channel is equal to the width of thesurface channel. It will appreciated that different dimensions arepossible.

There may be multiple fill ports coupled to a single promotion port viaa common flow path 130. Different reactive agents may be introduced toeach of the fill ports for reaction within the flow path 130. The flowpath 130 may thus act as a reaction chamber activated by proximity ofthe surface 120. Similarly, there may be multiple promotion portsconnected to a common fill port via common flow path 130. Equally, theremay be multiple fill ports connected to multiple promotion ports via acommon flow path 130.

Referring to 11 and 12, multiple devices as herein before described withreference to FIGS. 7 to 10 may be integrated to form an array. Differentconfigurations of such an array are possible, involving differentnumbers of devices. The chambers of such arrays may be interconnected toform a cascade. Some of the interconnected chambers may provide reactionchambers in which liquid 110 reacts. The product of such reactions maybe analyzed in other chambers or on the surface 120. Such products maybe used to treat or react with the surface 120.

Referring now to FIG. 13, a device as herein before described withreference to FIGS. 1 to 4 may be employed to trace liquid 110 across thesurface 120 via planar movement of the device relative to the surface120 with the end 80 of the device in contact with the surface 120.Referring to FIG. 14, a trail of liquid 110 is thus left on the surface.

Similarly, with reference to FIG. 15, a device as herein beforedescribed with reference to FIGS. 5 and 6 may be employed to tracedifferent liquids across the surface 120, each liquid being loaded intoa different chamber 20 of the device. Referring to FIG. 16, dependingthe orientation and motion of the device relative to the surface 120,the different liquids can be mixed in selected regions of the surface120. Such mixing may, for example, facilitate localized reactionsbetween the liquids in selected regions of the surface 120. Equally adevice as herein before described with reference to FIGS. 5 and 6 may beemployed to trace similar liquids across the surface in separate trails.Depending the orientation and motion of the device relative to thesurface 120, the trails can be separate or superimposed on each other.

A device as herein before described with reference to FIGS. 7 to 10 maybe likewise employed trace a flow of liquid 110 across the surface 120.Independent control of flow rate and tracing speed permits tuning of thesurface treatment applied via the device. Referring to FIG. 17, two ormore such devices may be mounted in an array as herein before describedwith reference to FIGS. 11 and 12. Such an array may also be employed totrace two liquid flows across the surface 120. Referring to FIG. 18, theliquid flows may comprise the same or different liquids. Again,depending the orientation and motion of the device relative to thesurface 120, the trails of the liquid flows can be separate orsuperimposed on each other. Independent control of the tracing speed andflow rate permits creation of gradients in, for example, adsorbedmolecules on the surface.

Referring to FIG. 19, in other embodiments of the present invention, thefirst aperture 31, the second aperture 32, and the intervening flow path130 may be nested. For example, in one such example of the presentinvention, the first aperture 31 is surrounded by the second aperture32. The inner surface forms an annular recess surrounding the secondaperture 32. The circumferential outer wall of the second aperture 32 isof limited wettability as herein before described. An annular flow path130 is disposed between the first aperture 31 and the second aperture32. In operation, once contact between the liquid 110 in the firstaperture 31 and the surface 120 to be treated is established, flow ofliquid 110 extends radially from first aperture 31 to the secondaperture 32. The second aperture 32 may be continuous or defined by aseries of circumferentially spaced openings each connecting to thepromotion port. It will be appreciated that the form of the firstaperture 31, the flow path 130, and the second aperture 32, need not becircular. Other examples of nested versions of the present invention mayhave different nested geometric forms, such as square, triangular, ormore complex nested geometric forms.

Embodiments of the present invention have been described herein withreference to devices having less and more wettable surfaces. In suchdevices, confinement of liquid 110 is achieved via interfacial tension.The interfacial tension is a function of surface tension, surfacewettability and geometrical parameters in combination. The associatedconfinement pressure can be achieved via a wettability differencebetween different device sides and device geometry. The confinementconditions are a function of contact angles of the liquid 110 with thefaces of the device, surface tension in the liquid 110, pressures andflow rates. Preferable confinement conditions are obtained bysuperposing a wettability pattern on the geometry.

1. A device for applying a liquid to a substrate surface, the device comprising: a first chamber for carrying the liquid; a second chamber for carrying the liquid; a first aperture in the first chamber for communicating liquid from the first chamber to the substrate surface via a first conduit having outer sides of limited wettability to the liquid; a second aperture in the second chamber for communicating liquid from the second chamber to the substrate surface via a second conduit having outer sides of limited wettability to the liquid; a body including a protrusion defined by the outer sides of the first and second conduits, wherein the body comprises a plane inner surface surrounding the protrusion and a plane outer surface parallel to, offset from, and surrounding the inner surface, the protrusion extending from the inner surface and having an end coplanar with the outer surface, wherein the end of the protrusion is wettable by the liquid, and wherein the end of the protrusion comprises a flow path extending from the first aperture to the second aperture.
 2. A device as claimed in claim 1, wherein the first and second conduits comprise inner sides wettable by the liquid.
 3. A device as claimed in claim 1, wherein the inner surface forms a peripheral recess surrounding the protrusion.
 4. A device as claimed in claim 1, wherein the outer surface is of limited wettability to the liquid.
 5. A device as claimed in claim 1, wherein: the first chamber has a first pressure for retaining the liquid when the flow path is remote from the substrate surface; the second chamber has a second pressure such that the difference between the first and second pressures is oriented to promote flow of the liquid from the first chamber to the second chamber via the flow path in response to the flow path being located proximal to the substrate surface and the liquid in the device contacting the substrate surface; and, the first and second pressures are such that the liquid is drawn towards at least the second chamber in response to withdrawal of the flow path from the substrate surface.
 6. A device as claimed in claim 5, wherein at least one of the first chamber and the second chamber comprises a capillary network for applying pressure to the liquid.
 7. A device as claimed in claim 6, wherein each capillary network comprises at least one of a plurality of parallel capillary members, a mesh, a porous material, and a fibrous material.
 8. A device as claimed in claim 1, comprising a plurality of first chambers each coupled to the flow path.
 9. A device as claimed in claim 1, comprising a plurality of second chambers each coupled to the flow path.
 10. A device as claimed in claim 1 wherein the flow path has one of a curved cross section and a rectangular cross section.
 11. A device as claimed in claim 5, wherein the first and second pressures are such that the liquid is drawn towards the first chamber and the second chamber in response to withdrawal of the flow path from the substrate surface.
 12. A device as claimed in claim 1, wherein the second aperture surrounds the first aperture.
 13. A device as claimed in claim 1 being of unitary construction.
 14. A device as claimed in claim 13, formed from any one of polymer, glass, silicon, SU-8, photoresist, thermoplastic, ceramic, and metal.
 15. A device as claimed in claim 1 being of layered construction.
 16. A device as claimed in claim 15, wherein each layer is formed from one of polymer, glass, silicon, SU-8, photoresist, thermoplastic, metal, and ceramics.
 17. An array of devices each as claimed in claim
 1. 18. A method for applying a liquid to a substrate surface, the method comprising: locating a device as claimed in claim 1 proximal to the substrate surface; supplying the liquid to the substrate surface via the device; flowing the liquid from the first chamber to the second chamber via the flow path; and, retracting the device from the substrate surface.
 19. A method as claimed in claim 18, further comprising varying the flow of the liquid from the first chamber to the second chamber during the supply of the liquid to the surface.
 20. A method as claimed in claim 18, further comprising: prior to the retracting, moving the device relative to the substrate surface with the liquid in the or each aperture contacting with the substrate surface.
 21. A method for applying a liquid to a substrate surface, the method comprising: locating a device as claimed in claim 8 proximal to the substrate surface; supplying the liquid to the substrate surface via the device; moving the device relative to the substrate surface with the liquid in the apertures contacting with the substrate surface; and, retracting the device from the substrate surface.
 22. A method for applying a liquid to a substrate surface, the method comprising: locating an array of devices as claimed in claim 17 proximal to the substrate surface; supplying the liquid to the substrate surface via the array; in each device of the array, flowing the liquid from the first chamber to the second chamber via the flow path; moving the array relative to the substrate surface with the liquid in each aperture contacting with the substrate surface; and, retracting the array from the substrate surface.
 23. A method as claimed in claim 22, further comprising, in at least one device of the array, varying the flow of the liquid from the first chamber to the second chamber during the supply of the liquid to the surface.
 24. A method as claimed in claim 22, comprising orienting the array relative to the substrate surface such that traces of the flows of liquid produced as the array is moved relative to the substrate surface remain separate.
 25. A method as claimed in claim 22, comprising orienting the array relative to the substrate surface such that traces of the flows of liquid produced as the array is moved relative to the substrate surface overlap.
 26. A method as claimed in claim 22, further comprising, prior to locating, loading a similar liquid into each device of the array.
 27. A method as claimed in claim 22, further comprising, prior to locating, loading different liquids into each device of the array. 